Barry Marshall (left) and Robin Warren

The Nobel Prize notice issued by Sweden’s Karolinska Institute last Tuesday congratulated this year’s winners in physiology and medicine, Dr Barry Marshall and Dr Robin Warren, for their “tenacity and a prepared mind to challenge prevailing dogmas.” But what the Nobel committee didn’t mention is that, as well as his mind, Marshall had nearly sacrificed his life to the cause he stood for. To convince sceptics that peptic ulcers and stomach inflammation are mostly caused by the bacteria Helicobacter pylori ? rather than stress or anxiety ? Marshall had swallowed the potentially deadly bug.

Although he’s the junior partner of the duo that has been honoured, Marshall is described by Warren as “a much better salesman” than himself. “If you make a big discovery, if you don’t sell it, it’s not going to be heard by anyone else,” he has told journalists who sought his comments on the the news from Stockholm.

“Dr Marshall’s deliberate self-infection was an extraordinary act that demonstrated outstanding dedication and commitment to his research,” admits Lord May of Oxford, president of Britain’s Royal Society, in a tribute to the maverick scientist.

Such tributes have indeed been hard-earned, as Marshall had risked his life, his job and his wife’s wrath to establish his radical theory overturning conventional medical thinking. “After a particularly frustrating time while presenting a paper [in a scientific meet], I decided that the way to answer the sceptics was an experiment to prove the bacterium could infect a healthy person ? myself,” Marshall has told Knowhow in an e-mail interview after winning the Nobel. “I felt a little nauseated after I drank the broth containing a suspended culture of [the bacteria] H. pylori. I then had some stomach rumblings for three days, followed by bloating and fullness after evening meals.”

According to him, he had no choice but use himself as a guinea pig because his attempts to infect lab animals with the bacteria somehow failed many a time. Snubbed by colleagues ? contemporary wisdom said no bug could survive the highly acidic stomach ? and ignored by pharmaceutical firms, which had been making fortunes selling acid-blockers and anti-anxiety drugs meant to control ulcers, Marshall took this extreme step to prove his hypothesis.

Five days after drinking the broth he became ill with an early-morning nausea, vomiting acid-free gastric juice and having a “putrid” breath. “Actually, I only developed gastritis ? but it was rather severe ? so the main goal of the experiment had been reached. I did not develop an ulcer and my immune system cured the infection after two weeks,” Marshall has told Knowhow. The gastric biopsy of his stomach lining found the telltale inflammation with thousands of H. pylori bacteria.

However, the medical community, sceptical of Marshall’s ideas and critical of his unorthodox experimental technique, largely rejected his theory until the experiment was repeated and several publications confirmed that the hypothesis was correct.

Although Marshall’s pugnacious attitude helped establish the radical idea ? and now given a stamp of approval by the Nobel committee ? self-experimenters have become a rarity in modern medicine. “There have been several instances of self-experiments in the history of medicine,” says Dr Pradeep Seth, a former head of microbiology at the All India Institute of Medical Sciences (AIIMS), New Delhi. Seth, too, had injected himself with an experimental HIV vaccine that he had been designing since 1996. Having already tested the vaccine in animals, Seth was eager to know the human body’s reaction to the shot as human trials were not expected to start until 2005.

“The test was to find out if the vaccine construct was going to evoke any severe immune reaction,” he remarked. India’s medical community, however, condemned Seth’s endeavour as unethical, because the vaccine was yet to be cleared for human trials.

Medical history abounds with mavericks such as Marshall and Seth, who have risked their lives, not to speak of incredulity and derision from peers, to further science. Giant leaps in modern medicine owe a great deal to many such dedicated doctors, who, madly driven by their urge to fathom the depths of many diseases, subjected themselves to such risks. Without self-experimentation we might never have learned the true nature of many diseases, drugs or vaccines might not have been developed, risky surgical procedures may have been abandoned, and revolutionary diagnostic techniques may have never been tried on humans.

According to Lawrence Altman, New York Times’ medical writer and author of Who Goes First? The Story of Self-Experimentation in Medicine, self-experiment is a “historical tradition” that is much more widespread in medicine than acknowledged.

The most famous exercise in self-experimentation in the history of medicine involves Sir John Hunter, the 18th-century English anatomist and surgeon. He inoculated himself with venereal pus from a prostitute. No wonder he developed both gonorrhoea and syphilis, and eventually died of the latter. His self-sacrifice helped decipher the sexual transmission route of the venereal diseases.

Another celebrated self-experimenter was the 19 th century German researcher Max von Pettenkofer who drank a test tube full of cholera bacteria in his zeal to show that environmental factors, rather than germs alone, caused the disease. Of course, he was wrong, and paid a heavy price for his erroneous ideas. He fell ill and narrowly escaped death. German surgeon Werner Forssmann, in 1929, inserted a tube into his own heart to find out if drugs could be administered directly into the organ during emergencies. This risky technique remained unnoticed until New York surgeons Andr? Cournand and Dickinson Richards refined it in the 1940s as groundbreaking work in cardiorespiratory physiology. In 1956, all three were awarded the Nobel prize (for physiology and medicine). Although cases of self-experiments were quite common till the 1960s, the trend gradually declined and is now extremely rare.

What motivated Marshall to revive that not-so-old tradition? “In my case, I had less patience with sceptics who often did not know very much about the subject,” he has told Knowhow. He had realised that “entrenched opinions were not based on scientific fact, but were more like religious beliefs.” He was determined to change that.

According to Altman, it’s not just the spirit of adventure or lure of first-hand experience that encourages medical scientists to embrace fatal risks. The self-experimenters believe that being their own guinea pigs can help avoid frustrating efforts to recruit volunteers and going through the nitty-gritty of informed consent. It also makes it easier to adhere to research protocols and generate data which are more reliable, because the researcher is able to monitor the project more closely.

However, self-experiments also have some inherent problems. “It’s important to be objective in science, and this may not be ensured in self-experiments, because the researcher himself or herself is involved in the test,” says Prof. Robert Moots, director of research and development at the Clinical Science Centre, University of Liverpool, UK. “Self-experimentation is not only unethical, but also fraught with biases,” says Dr Samiran Nundy, head, department of academics and research, Sir Ganga Ram Hospital, New Delhi. “The trend of self-experimentation has declined not because of a lack of dedication, but growth of a more rational approach to medical research.”

In spite of the shortfalls, researchers who sacrifice themselves at the altar of medical science should not be denounced as irrational or mad. The romantic spirit of adventure, driven by altruism, may look alien in the modern era of impersonal and mechanistic medicine, but doctors such as Marshall may inspire future young researchers.

Altman aptly sums up the situation in Who Goes First? “Why call self-experimentation foolish when we climb mountains, become test pilots, build bridges and skyscrapers?” He continues, “In any experiment, the outcome is not known ahead of time. If the researcher claims there is no risk, why is the researcher unwilling to try it? Doctors’ lives are no more valuable than those of the other members of society whom they ask to volunteer for their research.”